CN109475684B

CN109475684B - Medicament delivery system

Info

Publication number: CN109475684B
Application number: CN201780043198.3A
Authority: CN
Inventors: B·弗兰克; B·福里斯; S·沃拉克; I·麦尔兹
Original assignee: Sanofi SA
Current assignee: Sanofi SA
Priority date: 2016-07-14
Filing date: 2017-07-12
Publication date: 2022-02-01
Anticipated expiration: 2037-07-12
Also published as: US20220054743A1; US11185628B2; JP2019520931A; JP6972100B2; WO2018011258A1; US20190282752A1; EP3484543A1; CN109475684A

Abstract

A medicament delivery system for use with a medicament delivery device includes a support member, a compression member spaced from the support member to define a gap therebetween, a mechanical coupling between the support member and the compression member and including a plurality of connecting members extending between the support member and the compression member, and a biasing element connected to the compression member and configured to apply a rotational force to the compression member relative to the support member. The mechanical coupling is configured such that rotation of the compression member relative to the support member causes the compression member to be pulled toward the support member to reduce the gap between the compression member and the support member.

Description

Medicament delivery system

Technical Field

The present invention relates to a system for delivering a liquid medicament, in particular for use with a medical injector device.

Background

There are a number of diseases that require conventional treatment by injection of a medicament. Injection devices known in the art include infusion pumps and patch pumps for delivering injections of medicaments. Another type of injection device is a bolus injector device. Some biopharmaceuticals contain injectable liquids of higher viscosity and are administered in larger volumes than traditional liquid pharmaceuticals, typically at least 1ml, and possibly a few ml. Such high volume bolus injectors may be referred to as Large Volume Devices (LVDs). Such an injection device may be initially supported on the patient at the appropriate injection site and, once installed, the injection is initiated by the patient or other person (user).

The drug delivery process of such devices may last from minutes to hours, particularly in the case of large volume devices. However, for effective treatment of medical conditions, it is important that the device reliably and completely deliver the entire dose of medicament to the patient.

Disclosure of Invention

The present invention provides a medicament delivery system for use with a medicament delivery device, comprising a support member, a compression member spaced from the support member to define a gap therebetween, a mechanical coupling between the support member and the compression member and comprising a plurality of connecting members extending between the support member and the compression member, and a biasing element connected to the compression member and configured to apply a rotational force to the compression member relative to the support member, wherein the mechanical coupling is configured such that rotation of the compression member relative to the support member causes the compression member to be drawn towards the support member to reduce the gap between the compression member and the support member.

Each connecting member may be pivotally connected to the support member and the compression member.

Each connecting member may be pivotably connected to the support member and the compression member by a ball-and-socket coupling. This may advantageously facilitate the rotational movement of the compression member relative to the support member.

The connecting member may comprise an inextensible rigid rod. This may advantageously facilitate constant translation of the compression member relative to the support member as the compression member rotates.

The biasing element may also be configured to bias the compression member toward the support member. This may advantageously facilitate compression of the body between the support member and the compression member.

The biasing member may comprise a helical torsion spring. This may advantageously facilitate the rotational biasing of the compression member.

The helical torsion spring may be conical in shape. This may advantageously facilitate compact and/or space efficient packaging of the biasing member (e.g. within the medicament delivery device).

The support member and the compression member may comprise substantially parallel spaced apart plates. This may advantageously facilitate retention of the body between the plates.

The medicament delivery system may additionally comprise a telescopic medicament reservoir arranged in the gap between the support member and the compression member. This may advantageously facilitate containment and delivery of the medicament.

The present invention additionally provides a medicament delivery device comprising a housing, a medicament delivery system as described above arranged in the housing and an injection needle in fluid connection with the medicament reservoir.

The medicament delivery device may comprise a releasable locking mechanism configured to retain the compression member against the biasing force of the biasing element. This may advantageously facilitate holding the compression member away from the support member until the medicament delivery process is to be initiated.

The locking mechanism may include an actuator operable to release the compression member to move from the extended state to the compressed state under the biasing force of the biasing element. This may advantageously facilitate initiation of the medicament delivery process.

The medicament delivery device may additionally include a needle control mechanism configured to move the needle between a retracted position in which the needle is disposed within the housing and an extended position in which the needle protrudes from the housing. This may advantageously facilitate preventing exposure of the needle until the medicament delivery process is to be initiated.

The medicament reservoir may contain a liquid medicament.

The present invention additionally provides a method of operating a medicament delivery system for use with a medicament delivery device, the medicament delivery system comprising a support member, a compression member spaced from the support member to define a gap therebetween, a telescopic medicament reservoir disposed within the gap, a mechanical coupling between the support member and the compression member and comprising a plurality of connecting members extending between the support member and the compression member, and a biasing element connected to the compression member, the method comprising: the biasing member applies a rotational force to the compression member relative to the support member; the mechanical coupling translates rotation of the compression member relative to the support member to move the compression member toward the support member to reduce the gap therebetween; and causing the medicament reservoir to telescope to expel the liquid medicament from the medicament reservoir.

Drawings

Embodiments of the invention will now be described, by way of example only, with reference to the accompanying drawings, in which:

fig. 1 shows a schematic cross-sectional view of a medicament injection device according to an embodiment of the present invention comprising a medicament delivery system according to an embodiment of the present invention;

fig. 2 shows a perspective view of the medicament delivery system of fig. 1 without a medicament container in an extended state;

fig. 3 shows a perspective view of the medicament delivery system of fig. 1 comprising a medicament container in an extended state;

fig. 4A and 4B show a side view and a perspective view, respectively, of the medicament delivery system of fig. 2 in an extended state;

figures 5A and 5B show side and perspective views, respectively, of the medicament delivery system of figure 2 in a partially compressed state;

fig. 6A and 6B show a side view and a perspective view, respectively, of the medicament delivery system of fig. 2 in a fully compressed state; and

fig. 7 shows a schematic cross-sectional view of a medicament injection device according to another embodiment of the present invention comprising a medicament delivery system according to an embodiment of the present invention.

Detailed Description

The following describes a fluid medicament delivery device 1 for delivering a fluid medicament to a patient. As shown, the device 1 comprises a medicament injection device, but other types of medicament delivery devices are contemplated within the scope of the present invention. The device 1 comprises a medicament delivery system 2 for delivering a liquid medicament to a patient. The delivery system 2 may comprise a medicament reservoir 3 for storing a quantity of medicament. The device 1 is configured for use against the skin of a patient and for delivering a medicament by injection. The device 1 is described later in the context of a bolus injector, but it will be understood that it could alternatively be another type of Large Volume Device (LVD) or other medicament injection device.

Referring to fig. 1, the device 1 comprises a housing 4, in which housing 4 the delivery system 2 comprising the medicament reservoir 3 and other components of the device 1 (not fully shown) are arranged. The housing 4 is formed of molded plastic or other suitable material. The medicament reservoir 3 is provided as a flexible and/or telescopic container 3 which may contain a single dose of medicament. The medicament reservoir 3 may be replaceable to allow reuse of the device 1. Alternatively, the medicament reservoir 3 may be non-replaceable in the device 1, such that once the medicament in the medicament reservoir 3 has been expelled, the device 1 can no longer be used to deliver medicament but can only be discarded. This single use feature of the device 1 facilitates ease of operation and improves safety by ensuring that a patient does not mistakenly install an incorrectly replaced medicament reservoir 3.

The device 1 comprises an injection element for injecting a medicament from the device 1 into a patient. The injection element is explained later in the case of a hollow injection needle 5, as shown in fig. 1. However, other injection elements are contemplated within the scope of the present invention, as will be described later, but it will be understood that other types of injection elements may alternatively be used. The medicament is delivered through the needle 5. The proximal end (not shown) of the needle 5 is fluidly connected to the medicament reservoir 3. The needle 5 is thus arranged to receive medicament from the medicament reservoir 3. The needle 5 comprises a distal end 6, the distal end 6 protruding, in use, through the housing 4 of the device 1 into the body tissue of the patient.

The injection needle 5 may be controllably extendable and/or retractable through the exterior of the housing 4 to allow it to be safely stowed in the housing 4 when not in use. Such a control mechanism is not shown in fig. 1, but is described below with reference to fig. 7, which illustrates an alternative embodiment of the present invention. Such a control mechanism may also include means to control the delivery of medicament from the medicament reservoir 3 through the needle 5, and/or may allow the needle 5 to automatically extend and retract during a medicament delivery procedure.

The housing 4 comprises a contact area 7, the contact area 7 being arranged to be used against the skin of a patient in use of the device 1. In the exemplary embodiment of fig. 1, the contact area 7 comprises a contact surface of the housing 4. The contact area 7 may have geometric and tactile properties selected to be comfortable when used against the skin of a patient. The contact area 7 comprises an aperture 8 through which aperture 8 the injection needle 5 protrudes into the body tissue of the patient during medicament delivery.

In use of the device 1, the contact region 7 is held against the skin of the patient by the fastener. The fastener is adapted to hold the contact area 7 in a stable position against the skin over a significant period of time (e.g. several hours) to ensure that the injection needle 5 is maintained in a fixed position relative to the patient's body during use of the device 1. The exemplary fastener shown in fig. 1 is an adhesive layer 9 for temporarily adhering the contact region 7 to the skin of a patient. The adhesive layer 9 may comprise a standard biocompatible glue, as used in conventional adhesive bandages. To protect the adhesive layer 9 from damage and to prevent it from adhering to undesired objects before attachment to the patient's skin, the contact area 7 of the device 1 may comprise a protective cover layer (not shown) covering the adhesive layer 9. The protective cover layer can be selectively removed from the contact areas 7, for example by peeling the cover layer off the adhesive layer 9, to expose the adhesive layer 9 before use of the device 1.

The medicament delivery system 2 of the medicament injection device 1 comprises a support member in the form of a support plate 10 and a compression member in the form of a compression plate 11. The support plate 10 and the compression plate 11 are substantially parallel to and spaced apart from each other. The support member 10 and the compression member 11 are preferably substantially rigid planar components. In the embodiment shown, the support plate 10 and the compression plate 11 are circular and coaxial about a common axis X-X. A gap 12 is defined between the support plate 10 and the compression plate 11. The medicament reservoir 3 is arranged in the gap 12 and is contacted on both sides by the support plate 10 and the compression plate 11. The support member 10 is fixed relative to the housing 4. The compression member 11 is movable relative to the support member 10 and the housing 4.

The mechanical coupling connects the support plate 10 and the compression plate 11 in a manner that allows the compression plate 11 to rotate relative to the support plate 10 about the axis X-X and also allows the compression plate 11 to move in the axial direction towards and away from the support plate 10. Furthermore, the mechanical coupling is configured such that rotation of the compression plate 11 relative to the support plate 10 causes the compression plate 11 to move towards and away from the support plate 10. The mechanical coupling comprises a plurality of connecting members in the form of rigid connecting rods 13. Each connecting rod 13 is connected at one end to the support plate 10 and at its other end to the compression plate 11. In the embodiment shown, the connection between the connecting rod 13 and the support plate 10/compression plate 11 comprises a ball-and-socket type joint. Each connecting rod 13 has a ball element 14 at each end. The support plate 10 and the compression plate 11 are each formed with a partially spherical socket 15, the partially spherical sockets 15 being configured to receive and rotationally retain the ball element 14 of the connecting rod 13.

The biasing member is arranged on the opposite side of the compression member 11 with respect to the medicament reservoir 3. The biasing member is configured to apply a rotational force to at least the compression member 11 to urge the compression member 11 to rotate relative to the support member 10. In the exemplary embodiment of the invention shown, the biasing member is in the form of a conical torsion spring 16. A first end 17 of the torsion spring 16 is fixed to the compression plate 11. The opposite, second end 18 of the torsion spring 16 is fixedly secured relative to the housing 4. The second end 18 may be fixedly secured to the housing 4 itself, or to a component or mechanism that is fixed relative to the housing 4. The conical torsion spring 16 may also be configured to urge the compression plate 11 to bias the compression plate 11 in a direction substantially along the axis X-X toward the support plate 10.

The device 1 comprises a locking mechanism 19, said locking mechanism 19 being configured to engage the compression plate 11 and/or the torsion spring 16 to hold the support plate 10 in position against the force of the torsion spring 16. A locking mechanism 19 may be provided in the housing 4 and the second end 18 of the torsion spring 16 may be secured to the locking mechanism 19. The locking mechanism 19 comprises a release button 20 accessible from the outside of the housing 4. The release button 20 may be operable by a user to disengage the locking mechanism 19 to release the compression plate 11/torsion spring 16, thereby allowing the compression plate 11 to move under the biasing force of the torsion spring 16.

The various stages of use of the medicament delivery system 2 are shown in more detail in figures 4A to 6B. As with fig. 2, fig. 4A to 6B show the medicament delivery system 2 without the medicament reservoir 3 for ease of illustration. Fig. 4A and 4B show the medicament delivery system in a fully deployed state. I.e. the support plate 10 and the compression plate 11 are separated by the maximum distance allowed by the connecting rod 13. In this configuration, the connecting rods 13 extend substantially perpendicular to the support plate 10 and the compression plate 11. Accordingly, the respective spherical sockets 15 in the support plate 10 and the compression plate 11 are aligned in the axial direction. In the fully extended state, the gap 12 is thus at its largest size and accommodates the medicament reservoir 3 when filled with medicament. Fig. 3 shows such a configuration, in which the torsion spring 16 is omitted.

Fig. 5A and 5B show the medicament delivery system 2 in a partially compressed state. Here, the torsion spring 16 has been released by the locking mechanism 19 and pushes the compression plate 11 in the rotational direction about the axis X-X relative to the support plate 10. Thereby, the compression plate 11 is caused to rotate relative to the support plate 10 in the direction indicated by the arrow a'. This causes the respective spherical sockets 15 in the support plate 10 and the compression plate 11 to be offset in the direction of rotation about the axis X-X. Since the connecting rods 13 are rigid and inextensible, this causes the compression plate 11 to be pulled towards the support plate 10, so that the size of the gap 12 is reduced. This causes the medicament reservoir 3 to compress and the medicament therein to be expelled from the medicament reservoir through the needle 5 into the patient.

Fig. 6A and 6B show the medicament delivery system 2 in a fully compressed state. Here, the torsion spring 16 continuously pushes the compression plate 11 in the rotational direction about the axis X-X in the direction of the arrow 'a' with respect to the support plate 10. The compression plate 11 has been pulled further towards the support plate 10, thereby further reducing the size of the gap 12. The medicament reservoir 3 arranged in the gap 12 will thus have been further compressed and the entire dose of medicament therein will have been expelled from the medicament reservoir 3 through the needle 5 into the patient. As described above, the torsion spring 16 may also urge the compression plate 11 in the axial direction toward the support plate 10 and apply a rotational force. This may advantageously further urge the medicament delivery system into a compressed state, thus assisting in compressing the medicament reservoir 3 to expel medicament therein.

The operation of the medicament injection device 1 will now be described. The user initially removes the protective cover layer from the adhesive layer 9 and applies the device 1 to the intended injection site with the contact area 7 facing the patient's body. The distal end 6 of the needle 5 pierces the patient's skin. This may be done by a control mechanism (not shown) moving the needle to the extended position or by placing the device 1 at the injection site.

The release button 20 is pressed to disengage the locking mechanism 19. This releases the torsion spring 16 and/or the compression plate 11. The torsion spring 16 urges the compression plate 11 in a rotational direction about the axis X-X (as shown by arrow 'a' in fig. 5B and 6B). The compression plate 11 rotates about an axis X-X with respect to the support plate 10. However, since the connecting rods 13 are rigid and inextensible, the compression plate 11 is also caused to move toward the support plate 10 from the expanded state shown in fig. 4A and 4B to the partially compressed state shown in fig. 5A and 5B. The size of the gap 12 is thereby reduced and thus the flexible medicament reservoir 3 is squeezed between the support plate 10 and the compression plate 11. This causes the medicament in the medicament reservoir 3 to be expelled through the needle 5 into the patient.

The torsion spring 16 continuously pushes the compression plate 11 in a rotational direction so that it rotates with respect to the support plate 10 and moves toward the support plate 10. This continues through the partially compressed state shown in fig. 5A and 5B until the device reaches the fully compressed state shown in fig. 6A and 6B. Once in the fully compressed state, the medicament reservoir 3 is retracted to the point where the full dose of medicament has been expelled through the needle 5 into the patient. The device 1 may then be removed from the patient's body and discarded, or if it is a refillable reusable device/mounted replacement medicament reservoir, the device 1 may be saved for reuse.

Fig. 7 shows an alternative embodiment of a medicament injection device 1' of the present invention comprising a medicament delivery system 2 of the present invention. Similar features common to the embodiment shown in fig. 1 retain the same reference numerals and the description thereof will not be repeated. The embodiment shown in fig. 7 illustrates a control mechanism 21 configured to extend and retract the injection needle 5 and to control the medicament injection process. The control mechanism 21 may comprise a control unit 22 connected to the needle 5. The needle 5 may be connected to a control unit 22 via a valve 23 to allow control of the flow of medicament. A conduit 24 fluidly connects the outlet of the medicament reservoir 3 to the needle 5 via the control unit 22 and the valve 23.

The control unit 22 is mounted on the piston 25 to allow the needle 5 to move between the retracted position and the extended position, as indicated by arrow 'B' in fig. 7. In the retracted position, the needle is housed in the housing 4. In the extended position, the needle 5 extends through the hole 8 in the contact area 7. An injector spring 26 is provided to provide an additional biasing force to assist the needle 5 in moving to the extended position and piercing the patient's skin. An actuator 27 is provided on the housing 4 and is connected to the control unit 22. The actuator may include a button, switch, or other suitable component. Pressing the actuator 27 causes the control unit 22 to move the injection needle 5 to the extended position, ready to start a medicament delivery process by pressing the release button 20, as previously described. In an alternative embodiment, however, the locking mechanism 19 may be connected to the control unit 22 (as shown in dashed lines in fig. 7). In such an embodiment, the actuator 27 may be omitted. In such an embodiment, pressing the release button 20 will cause the control unit 22 to move the needle 5 to the extended position and will also start the medicament delivery of the medicament delivery system 2 as described earlier. The medicament flow through the needle 5 can be controlled by the control unit 22 by opening the valve 23 immediately when the needle 5 is completely inserted into the body tissue of the patient. It will be appreciated that in such an embodiment, the needle injection step and the medicament delivery step will not be two separate steps to be performed by the user.

The control mechanism 21 may be electrically driven. For example, the piston 25 may be electrically driven. The power may also be used to retract the syringe spring 26, the control unit 22 and the needle 5 to the retracted position, thereby withdrawing the needle 5. To this end, the control mechanism 21 may include an electric motor (not shown) and a suitable drive mechanism (not shown) coupled to the piston 25. The power may be provided by a battery (not shown) or by another power source in the device 1 that is rechargeable.

The control unit 22 may include an electronic controller (not shown) configured to control damage to various components of the device 1. In an alternative embodiment, the control unit operates under the control of a timing element (such as a mechanical timer). The timing element may be a countdown timer. The elapse of the countdown period of time by the timing element may indicate that an event has occurred, such as completion of an injection of a dose of medicament. The lapse of said countdown period may cause the piston 25 to move the needle 5, e.g. to withdraw the needle back into the housing 4 of the device 1.

Examples of alternative injection elements contemplated as within the scope of the present invention include hollow needles that may be sharpened to facilitate their insertion into the body tissue of a patient. It is possible to provide a separate needle (not shown) or trocar (not shown) to assist insertion of the distal end of the hollow needle into the body tissue. The needle may be controllably extended and/or retracted from the housing 4 of the device 1 in a similar manner to the hollow injection needle 5 described above. The needle may be configured to pierce the skin of the patient to allow the hollow needle to move into the body tissue. The needle may for example be arranged to extend through the centre of the hollow needle. Once the skin has been pierced, the device 1 may be configured to retract the needle into the housing prior to medicament delivery. In the case where the device 1 comprises a separate needle of the type described above, the device may comprise an actuator to facilitate extension and retraction of the needle.

It will be appreciated that the inventive concepts of the medicament delivery system of the present invention are applicable to LVDs. However, the invention is not intended to be limited to this particular type of medicament delivery device and the invention is intended to cover alternative types of medicament delivery devices comprising a medicament container to be received in a medicament delivery device (which may include, but is not limited to, patch pumps and infusion pumps).

The terms "drug" or "agent" are used interchangeably herein to mean a pharmaceutical formulation that includes at least one pharmaceutically active compound.

The term "drug delivery device" should be understood to encompass any type of device, system or apparatus designed to dispense a drug into a human or non-human body (veterinary applications are expressly contemplated by this disclosure). By "immediate dispensing" is meant that there is no necessary intermediate operation of the drug between its expulsion from the drug delivery device and its administration to the human or non-human body. Without limitation, typical examples of drug delivery devices may be found in injection devices, inhalers and gastric tube supply systems. Also without limitation, exemplary injection devices may include, for example, syringes, autoinjectors, injection pen devices, and spinal injection systems.

Those skilled in the art will appreciate that modifications (additions and/or removals) of various components/components of the substances, formulations, apparatuses, methods, systems and embodiments described herein may be made without departing from the full scope and spirit of the present invention, which encompasses such modifications and any and all equivalents thereof.

The term "drug" or "agent" is used herein to describe one or more pharmaceutically active compounds. As described below, a drug or medicament may include at least one small or large molecule or combination thereof of a variety of formulation types for treating one or more diseases. Exemplary pharmaceutically active compounds may include small molecules; a polypeptide; peptides and proteins (e.g., hormones, growth factors, antibodies, antibody fragments, and enzymes); sugars and polysaccharides; and nucleic acids, double-or single-stranded DNA (including naked and cDNA), RNA, antisense nucleic acids such as antisense DNA and RNA, small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. The nucleic acid may be incorporated into a molecular delivery system such as a vector, plasmid or liposome. Mixtures of one or more of these agents are also contemplated.

The term "drug delivery device" shall cover any type of device or system configured to dispense a drug into the body of a human or animal. Without limitation, the drug delivery device may be an injection device (e.g., syringe, pen-type injector, autoinjector, bulk device, pump, infusion system, or other device configured for intraocular, subcutaneous, intramuscular, or intravascular delivery), a dermal patch (e.g., osmotic, chemical, microneedle), an inhaler (e.g., for the nose or lung), an implantable device (e.g., a coated stent, capsule), or a delivery system for the gastrointestinal tract. The medicaments described herein may be particularly useful with injection devices that include a needle (e.g., a small gauge needle).

The medicament or medicament may be contained within a primary package or "drug container" suitable for use with the drug delivery device. The drug container may be, for example, a cartridge, syringe, reservoir, or other container configured to provide a suitable chamber for storing (e.g., short-term or long-term storage) one or more pharmaceutically active compounds. For example, in some cases, the chamber may be designed to store the drug for at least one day (e.g., 1 day to at least 30 days). In some cases, the chamber may be designed to store the drug for about 1 month to about 2 years. Storage may be at room temperature (e.g., about 20 ℃) or at freezing temperatures (e.g., about-4 ℃ to about 4 ℃). In some instances, the drug container may be or include a dual-chamber cartridge configured to separately store two or more components of a pharmaceutical formulation (e.g., a drug and a diluent, or two different types of drugs), one component for each chamber. In such cases, the two chambers of the dual-chamber cartridge may be configured to allow mixing between two or more components of a drug or medicament prior to and/or during dispensing into the human or animal body. For example, the two chambers may be configured such that they are in fluid communication with each other (e.g., via a conduit between the two chambers) and allow the two components to be mixed when desired by a user prior to dispensing. Alternatively or additionally, the two chambers may be configured to allow mixing while the components are being dispensed into the human or animal body.

The drug delivery devices and drugs described herein may be used to treat and/or prevent a variety of different types of conditions. Exemplary conditions include, for example, diabetes or complications associated with diabetes such as diabetic retinopathy, thromboembolic conditions such as deep vein or pulmonary thromboembolism. Other exemplary conditions are Acute Coronary Syndrome (ACS), angina pectoris, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis. Exemplary drugs for treating and/or preventing diabetes or complications associated with diabetes include insulin, such as human insulin or a human insulin analogue or derivative, glucagon-like peptide (GLP-1), GLP-1 analogue or GLP-1 receptor agonist, or an analogue or derivative thereof, dipeptidyl peptidase-4 (DPP4) inhibitor or a pharmaceutically acceptable salt or solvate thereof, or any mixture thereof. The term "derivative" as used herein refers to any substance that is structurally similar enough to the original substance to have a substantially similar function or activity (e.g., therapeutic efficacy).

Exemplary insulin analogs are Gly (a21), Arg (B31), Arg (B32) human insulin (insulin glargine); lys (B3), Glu (B29) human insulin; lys (B28), Pro (B29) human insulin; asp (B28) human insulin; human insulin, wherein proline at position B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein Lys at position B29 is replaced by Pro; ala (B26) human insulin; des (B28-B30) human insulin; des (B27) human insulin and Des (B30) human insulin.

Exemplary insulin derivatives are, for example, B29-N-myristoyl-Des (B30) human insulin; B29-N-palmitoyl-Des (B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29 human insulin; B28-N-palmitoyl-LysB 28ProB29 human insulin; B30-N-myristoyl-ThrB 29LysB30 human insulin; B30-N-palmitoyl-ThrB 29LysB30 human insulin; B29-N- (N-palmitoyl- γ -glutamyl) -Des (B30) human insulin; B29-N- (N-lithocholyl- γ -glutamyl) -Des (B30) human insulin; B29-N- (. omega. -carboxyheptadecanoyl) -Des (B30) human insulin and B29-N- (. omega. -carboxyheptadecanoyl) human insulin. Exemplary GLP-1, GLP-1 analogs, and GLP-1 receptor agonists are, for example: Lixisenatide/AVE 0010/ZP10/Lyxumia, Exenatide/Exendin-4 (Exendin-4)/Byetta/Bydureon/ITCA 650/AC-2993 (a 39 amino acid peptide produced by the Geranium salivary gland), Liraglutide/Victorza, Semaglutide, Taspoglilutide, Syncrita/Albiglutide (Abiutatai), Dulaglutide (D.glycopeptide), rExendin-4, CJC-1134-PC, PB-1023, TTP-054, Langlertide/112C, CM-3, GLP-1Eligen, ORD-090-631, Node-9924, NN-9926, GLP-27, Vicker-0010, ZJ-091-Z-092, MAR-K-095, MAR-3027, Glyd-1-O-D-092, MAR-M-3052, MAR-D-305, MAR-M-D-1, and MAR-302, MAR709, ZP-2929, ZP-3022, TT-401, BHM-034, MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, Exenatide-XTEN, and Glucagon-XTEN.

An exemplary oligonucleotide is, for example, mipomensen/Kynamro, a cholesterol-lowering antisense therapy for the treatment of familial hypercholesterolemia.

Exemplary DPP4 inhibitors are Vildagliptin (Vildagliptin), Sitagliptin (Sitagliptin), Denagliptin (dinagliptin), Saxagliptin (Saxagliptin), Berberine (Berberine). Exemplary hormones include pituitary or hypothalamic hormones or regulatory active peptides and antagonists thereof, such as gonadotropin (Gonadotropine) (Follitropin), luteinizing hormone (Lutropin), chorionic gonadotropin (cholongonadotropin), menotrophin (Menotropin), Somatropin (Somatropin), Desmopressin (Desmopressin), Terlipressin (Terlipressin), Gonadorelin (Gonadorelin), Triptorelin (Triptorelin), leuprolide (Leuprorelin), Buserelin (Buserelin), Nafarelin (Nafarelin), and Goserelin (Goserelin).

Exemplary polysaccharides include glycosaminoglycans, hyaluronic acid, heparin, low or ultra-low molecular weight heparin or derivatives thereof, or sulfated polysaccharides such as polysulfated forms of the above polysaccharides and/or pharmaceutically acceptable salts thereof. An example of a pharmaceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium (enoxaparin sodium). An example of a hyaluronic acid derivative is Hylan G-F20/synechol (Synvisc), a sodium hyaluronate.

The term "antibody" as used herein refers to an immunoglobulin molecule or antigen-binding portion thereof. Examples of antigen-binding portions of immunoglobulin molecules include F (ab) and F (ab')2 fragments, which retain the ability to bind antigen. The antibody may be polyclonal, monoclonal, recombinant, chimeric, de-immunized or humanized, fully human, non-human (e.g., murine), or single chain. In some embodiments, the antibody has effector function and can fix complement. In some embodiments, the antibody does not have or has a reduced ability to bind Fc receptors. For example, the antibody may be of the same type or subtype, an antibody fragment or mutant which does not support binding to an Fc receptor, e.g. which has a mutagenized or deleted Fc receptor binding region.

The term "fragment" or "antibody fragment" refers to a polypeptide derived from an antibody polypeptide molecule (e.g., an antibody heavy and/or light chain polypeptide) that does not comprise a full-length antibody polypeptide but still comprises at least a portion of a full-length antibody polypeptide that is capable of binding an antigen. An antibody fragment can comprise a cleavage portion of a full-length antibody polypeptide, but the term is not limited to such a cleavage fragment. Antibody fragments useful in the present invention include, for example, Fab fragments, F (ab')2 fragments, scFv (single chain Fv) fragments, linear antibodies, monospecific or multispecific antibody fragments such as bispecific, trispecific and multispecific antibodies (e.g., diabodies, triabodies, tetrabodies), minibodies, chelating recombinant antibodies, trifunctional antibodies (tribods) or bifunctional antibodies (bibodies), intrabodies, nanobodies, Small Modular Immunopharmaceuticals (SMIPs), binding domain immunoglobulin fusion proteins, camelized antibodies, and VHH-containing antibodies. Other examples of antigen-binding antibody fragments are known in the art.

The term "complementarity determining region" or "CDR" refers to a short polypeptide sequence within the variable regions of both heavy and light chain polypeptides that is primarily responsible for mediating specific antigen recognition. The term "framework region" refers to amino acid sequences within the variable regions of both heavy and light chain polypeptides that are not CDR sequences and are primarily responsible for maintaining the correct positioning of the CDR sequences to allow antigen binding. As is known in the art, some residues within certain antibody framework regions may be directly involved in antigen binding or may affect the ability of one or more amino acids in the CDRs to interact with antigen, although the framework regions themselves are not directly involved in antigen binding.

Exemplary antibodies are anti-PCSK-9 mAbs (e.g., Alirocumab), anti-IL-6 mAbs (e.g., Sarilumab), and anti-IL-4 mAbs (e.g., Dupilumab).

The compounds described herein may be used in a pharmaceutical formulation comprising (a) the compound or a pharmaceutically acceptable salt thereof and (b) a pharmaceutically acceptable carrier. The compounds may also be used in pharmaceutical formulations containing one or more other active pharmaceutical ingredients, or in pharmaceutical formulations in which a compound of the invention, or a pharmaceutically acceptable salt thereof, is the only active ingredient. Accordingly, the pharmaceutical formulations of the present invention encompass any formulation made by admixing a compound described herein and a pharmaceutically acceptable carrier.

Pharmaceutically acceptable salts of any of the drugs described herein are also contemplated for use in drug delivery devices. Pharmaceutically acceptable salts are, for example, acid addition salts and basic salts. Acid addition salts are, for example, the HCl or HBr salts. Basic salts are, for example, salts with alkali metal or alkaline earth metal cations selected from the group consisting of: for example Na + or K +, or Ca2+, or the ammonium ion N + (R1) (R2) (R3) (R4), wherein R1-R4 independently of one another mean: hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, and optionally substituted C6-C10 aryl, or optionally substituted C6-C10 heteroaryl. Other examples of pharmaceutically acceptable salts are known to those skilled in the art.

Pharmaceutically acceptable solvates are for example hydrates or alkanoates such as metholates or ethoxides.

Those skilled in the art will appreciate that modifications (additions and/or deletions) may be made to the various components/parts of the substances, formulations, devices, methods, systems and embodiments described herein without departing from the full scope and spirit of the invention, which encompasses such modifications and any and all equivalents thereof.

Claims

1. A medicament delivery system for use with a medicament delivery device, the medicament delivery system comprising:

a support member;

a compression member spaced apart from the support member to define a gap therebetween;

a mechanical coupling between the support member and the compression member, the mechanical coupling comprising a plurality of connecting members extending between the support member and the compression member; and

a biasing element connected to the compression member and configured to apply a rotational force to the compression member relative to the support member;

wherein the mechanical coupling is configured such that rotation of the compression member relative to the support member causes the compression member to be pulled toward the support member to reduce the gap between the compression member and the support member.

2. The medicament delivery system according to claim 1, wherein each connecting member is pivotably connected to the support member and the compression member.

3. The medicament delivery system according to claim 2, wherein each connecting member is pivotably connected to the support member and the compression member by a ball-and-socket coupling.

4. A medicament delivery system according to claim 2 or 3, wherein the connecting member comprises an inextensible rigid rod.

5. The medicament delivery system according to any one of claims 1 to 3, wherein the biasing element is further configured to bias the compression member towards the support member.

6. A medicament delivery system according to any one of claims 1 to 3, wherein the biasing element comprises a helical torsion spring.

7. The medicament delivery system according to claim 6, wherein the helical torsion spring is conical in shape.

8. The medicament delivery system according to any one of claims 1 to 3, wherein the support member and the compression member comprise substantially parallel spaced apart plates.

9. The medicament delivery system according to any one of claims 1 to 3, further comprising a telescopic medicament reservoir arranged in the gap between the support member and the compression member.

10. A medicament delivery device comprising a housing, a medicament delivery system according to claim 9 arranged within the housing, and an injection needle in fluid connection with the medicament reservoir.

11. The medicament delivery device of claim 10, comprising a releasable locking mechanism configured to retain the compression member against a biasing force of a biasing element.

12. A medicament delivery device according to claim 11, wherein the locking mechanism comprises an actuator operable to release a compression member to move from an extended state to a compressed state under the biasing force of the biasing element.

13. The medicament delivery device according to any one of claims 10 to 12, further comprising a needle control mechanism configured to move a needle between a retracted position in which the needle is arranged within the housing and an extended position in which the needle protrudes from the housing.

14. A medicament delivery device according to any of claims 10 to 12, wherein the medicament reservoir contains a liquid medicament.